RT Journal Article
SR Electronic
T1 Identifiability and experimental design in perturbation studies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.03.931816
DO 10.1101/2020.02.03.931816
A1 Torsten Gross
A1 Nils Blüthgen
YR 2020
UL http://biorxiv.org/content/early/2020/02/03/2020.02.03.931816.abstract
AB Motivation A common strategy to infer and quantify interactions between components of a biological system is to deduce them from the network’s response to targeted perturbations. Such perturbation experiments are often challenging and costly. Therefore, optimising the experimental design is essential to achieve a meaningful characterisation of biological networks. However, it remains difficult to predict which combination of perturbations allows to infer specific interaction strengths in a given network topology. Yet, such a description of identifiability is necessary to select perturbations that maximize the number of inferable parameters.Results We show analytically that the identifiability of network parameters can be determined by an intuitive maximum flow problem. Furthermore, we used the theory of matroids to describe identifiability relationships between sets of parameters in order to build identifiable effective network models. Collectively, these results allowed to device strategies for an optimal design of the perturbation experiments. We benchmarked these strategies on a database of human pathways. Remarkably, full network identifiability was achieved with on average less than a third of the perturbations that are needed in a random experimental design. Moreover, we determined perturbation combinations that additionally decreased experimental effort compared to single-target perturbations. In summary, we provide a framework that allows to infer a maximal number of interaction strengths with a minimal number of perturbation experiments.Availability IdentiFlow is available at github.com/GrossTor/IdentiFlow.Contact nils.bluethgen{at}charite.de